| Abstract: |
Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician’s choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis. Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/ adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis. Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1–43.0) months. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49–1.10) and 0.64 (0.44–0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45–1.02) and 0.61 (0.41–0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3–5, 74% and 72%), respectively. Conclusion: Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC. Trial Registration: ClinicalTrials.gov Identifier: NCT03517449. © 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology. |
| Keywords: |
survival; adult; controlled study; human tissue; treatment response; aged; middle aged; human cell; major clinical study; overall survival; cancer recurrence; doxorubicin; advanced cancer; cancer combination chemotherapy; cancer growth; diarrhea; drug safety; drug withdrawal; hypertension; side effect; treatment duration; paclitaxel; chemotherapy; follow up; endometrial cancer; antineoplastic agent; endometrial neoplasms; endometrium cancer; progression free survival; multiple cycle treatment; neutrophil count; neoplasm recurrence, local; anemia; nausea; randomized controlled trial; stomatitis; vomiting; antineoplastic combined chemotherapy protocols; histology; monoclonal antibody; arthralgia; fever; rash; confidence interval; alanine aminotransferase; malaise; physicians; immunotherapy; drug therapy, combination; multicenter study; tumor recurrence; mismatch repair; physician; hazard ratio; phase 3 clinical trial; leukocyte count; neoadjuvant chemotherapy; hypothyroidism; epidemiology; hand foot syndrome; alopecia; endometrium tumor; proteinuria; platelet count; asian; decreased appetite; quinolines; quinoline derivative; clinical outcome; overall response rate; body weight loss; antibodies, monoclonal, humanized; nivolumab; phenylurea compounds; lenvatinib; carbanilamide derivative; humans; human; female; article; pembrolizumab; asia, eastern; far east
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